2-(substituted amino)quinolizinium bromides

ABSTRACT

2-(Substituted amino)quinolizinium bromides are useful antiinflammatory agents.

[Uited States Patent [191 Maid et a].

Dec. 24, 11974 Z-(SUBSTITUTED AMINO)QUINOLIZINIUM BROMIDES [75] Inventors: Robert J. Alaimo; Marvin M.

Goldenberg, both of Norwich, NY.

[73] Assignee: Morton-Norwich Prodlicts, Inc,

Norwich, N.Y.

[22] Filed: Dec. 26, 1973 [21] Appl. N0.: 431,140

Related US. Application Data [62] Division of Ser. No. 278,618, Aug. 17, 1972.

[52] US. Cl. 260/296 B, 260/156, 424/263 [51] Int. Cl C07d 31/42 Primary Examiner-A1an L. Rotman Attorney, Agent, or Firm-Anthony J. Franze [57] ABSTRACT 2-(Substituted amino)quinolizinium bromides are useful antiinflammatory agents.

1 Claim, No Drawings Z-(SUBSTITUTED AMINO)QUINOLIZINIUM BBOMIDES wherein R is hydrogen or methyl; R. is hydrogen or amino, and R is hydroxyethyl, 2,3-dihydroxypropyl, p-phenylazoanilino or m-trifluoromethylanilino.

The compounds of this invention possess marked anti-inflammatory activity. When administered perorally in aqueous suspension at a-dose of 300 mg/kg to rats which thereafter receive a subpla'nter injection of 0.05 ml. of a 1% solution of carrageen (Viscarin in the hindfoot, edema of the foot is greatly reduced. They are thus useful agents in combatting swelling and edema in animal tissue.

The method which is currently preferred for the preparation of the compounds of this invention consists in bringing together 2-bromo-6-methylquinolizinium bromide or 2-bromoquinolizinium bromide and the appropriate amine in a suitable solvent such as ethanol or isopropanol preferably under the influence of heat.

In order that this invention may be understood by and readily available to those skilled in the art the following illustrative examples are supplied.

EXAMPLE I 2-[ 1-[(2-hydroxyethyl)hydrazino]-6- methyllquinolizinium Bromide EXAMPLE ll 2-(2,3-Dihydroxypropylamino)quinolizi'nium Bromide To a solution of 2-bromoquinolizinium bromide (8.0 g, 0.03 mole) in ethanol (150 ml.) was added l-amino- 2,3-propanediol (4.0 g, 0.04 mole). The stirred mixture was boiled under reflux for 3 hours. Cooling of the reaction mixture in an ice bath along with vigorous scratching precipitated a dark redbrown solid. The product (5.0 g, 60%) was recrystallized from ethanol to provide salmon colored crystals which melted at 166168.

Anal.

Calcd. for C H BrN O C, 48.17; H, 5.05; Br,

26.71. Found: C, 48.42; H, 5.01; Br, 26.58; 26.64.

EXAMPLE III Z-(p-Phenylazoanilino)quinolizinium Bromide To a solution of 2-bromoquinolizinium bromide (15.0 g, 0.05 mole) in isopropanol (300 ml. )was added p-phenylazoaniline (18.0 g, 0.09 mole). The stirred mixture was boiled under reflux for 4.0 hours. The reaction mixture was chilled in an ice bath and the solid was removed by filtration, providing 10.0 g. of maroon powder. The supernatant solution provided 9.0 g. additional reddish powder, making the total yield 19.0 g. (90%). Recrystallization from isopropanol/ethanol and again from ethanol/ether provided a rust-colored powder melting at 239-240.

Anal.

Calcd. for C H, BrN C, 62.23; H, 4.23; N, 13.95;

Br, 19.72. Found: C, 61.94, 62.07; H, 4.23, 4.29: N, 13.6a,

EXAMPLE IV 2-(m-Trifluoromethylanilino)quinolizinium Bromide To a solution of 2-bromoquinolizinium bromide g, 0.15 mole) in ethanol (600 ml.) was added mtrifluoromethylaniline (50 g, 0.30 mole). The stirred mixturewas boiled under reflux for 5 hours, then treated with Darco and filtered. The product was precipitated with ether. The crude product weighed 42 g. (76%). Recrystallization from isopropanol/ether provided material that melted at 229-230.

Anal.

quinolizinium bromide. 

1. THE COMPOUND 2-(2,3DIHYDROXYPROPYLAMINO)QUINOLIZINIUM BROMIDE. 